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Fundamentals of General, Organic, and Biological Chemistry - Chapter 17 Carboxylic Acids

Carboxylic Acids and Derivatives: Properties and Names (Chapter 17)

Introduction to Carboxylic Acids and Their Derivatives

  • Carboxylic Acid Definition: A compound characterized by a carbonyl group (\text{C=O}) bonded to a hydroxyl group (\text{-OH}), forming a (\text{-COOH}) functional group.

  • Learning Objectives: The primary goals are to compare and contrast the structures, reactions, hydrogen bonding, water solubility, boiling points, and the acidity and basicity of carboxylic acids, esters, and amides. Additionally, students should be able to name these compounds from their structures and draw structures from their names.

Key Functional Group Distinctions

  • Carboxylic Acids: Possess a hydroxyl group (\text{-OH}) directly bonded to the carbonyl carbon (\text{C=O}).

  • Esters: Feature an ester group (\text{-OR}) bonded to the carbonyl carbon (\text{C=O}).

  • Amides: Have an amine group (\text{-NH}2, \text{-NHR'}, or \text{-NR'}2) bonded to the carbonyl carbon (\text{C=O}).

Physical Properties and Intermolecular Forces

  • Polarity and Structural Similarity: The physical properties of carboxylic acids, esters, and amides are significantly influenced by their polarity and the structural similarity of the \text{δ+} and \text{δ-} carbonyl group. This illustrates the principle of "structure = function."

  • Boiling Points: These molecules generally exhibit higher boiling temperatures compared to alkanes, primarily due to their ability to form hydrogen bonds (an electrostatic force).

  • Water Solubility of Carboxylic Acids:

    • Short-Chain: Carboxylic acids with saturated, straight-chain R groups up to four carbons (e.g., butyric acid) are typically water-soluble.

    • Medium-Chain: Those with up to nine carbons are volatile liquids.

    • Long-Chain: Beyond nine carbons, they become waxy solids.

Reactions of Carboxylic Acids

  • Carbonyl Group Substitution: Carboxylic acids and their derivatives can undergo a carbonyl group substitution reaction, where a group (\text{-Z}) replaces the hydroxyl group (\text{-OH}) bonded to the carbonyl carbon.

  • Ester Formation: Esters are commonly synthesized via this carbonyl-group substitution reaction.

  • Ester Hydrolysis: Esters can revert to their original carboxylic acids through a reverse reaction known as hydrolysis.

  • Acyl-Group: This term refers to the part of a carboxylic acid remaining after the removal of the hydroxyl group (\text{-OH}). It is represented as \text{R-CO-}. The R group can be an alkyl chain containing 1-22 carbons.

  • Acyl-Group Transfer Reaction: In biological chemistry, the carbonyl-group substitution reaction is also known as an acyl-group transfer reaction. These reactions are crucial in processes like lipid metabolism.

Acidity and Hydrogen Bonding

  • Acidity: Carboxylic acids are capable of releasing a proton (\text{H+}) from their carboxyl group (\text{-COOH}), establishing an acid-base equilibrium.

  • Hydrogen Bonding: Similar to alcohols, carboxylic acids can engage in hydrogen bonding due to their polar \text{δ-} and \text{δ+} groups, which explains their higher boiling points compared to non-hydrogen bonding compounds of similar molecular weight.

Nomenclature of Carboxylic Acids and Derivatives

Priority in Naming Functional Groups

  • When multiple functional groups are present in a molecule, a hierarchy determines the naming convention. The highest priority group is named first.

  • Hierarchy (decreasing priority):
    Carboxylic Acids > Esters > Amides > Aldehydes > Ketones > Alcohols > Thiols > Amines > Ethers > Alkenes > Alkynes > Alkanes

Naming Carboxylic Acids (IUPAC System)

  • Parent Alkane Rule: Replace the final \text{-e} of the corresponding parent alkane name with the suffix \text{-oic acid}. For example, propane becomes propanoic acid.

  • Structure Examples:

    • Propanoic acid (from Propane)

    • $3$-Methylbutanoic acid (from $3$-Methylbutane)

    • $2$-Hydroxypropanoic acid (from $2$-Hydroxypropane)

Common Naming of Carboxylic Acids

  • Greek Letters for Carbons: For common names, carbon atoms attached to the carboxylic group are identified using Greek letters instead of numbers.

  • Alpha ($\alpha$) Carbon: The carbon atom immediately adjacent to the carbonyl carbon (carbon $1$) is designated as the alpha ($\alpha$) carbon (which is carbon $2$ in IUPAC nomenclature).

  • Example: Pyruvic acid and amino acids use both numbered carbonyl carbons and labeled alpha/beta carbons to show structure.

Table 17.1: Common Carboxylic Acids

Structure

Common Name

\text{HCOOH}

Formic acid

\text{CH}_3\text{COOH}

Acetic acid

\text{CH}3\text{CH}2\text{COOH}

Propionic acid

\text{CH}3\text{CH}2\text{CH}_2\text{COOH}

Butyric acid

\text{CH}3\text{CH}2\text{CH}2\text{CH}2\text{COOH}

Valeric acid

\text{CH}3\text{(CH}2\text{)}_{16}\text{COOH}

Stearic acid

(\text{HOOC-COOH}

Oxalic acid

\text{HOOC-CH}_2\text{-COOH}

Malonic acid

\text{HOOC-CH}2\text{CH}2\text{-COOH}

Succinic acid

\text{HOOC-CH}2\text{CH}2\text{CH}_2\text{-COOH}

Glutaric acid

Salicylic Acid

  • Description: A colorless, bitter-tasting solid, it serves as the precursor for aspirin (acetylsalicylic acid).

  • Biological Role: Salicylic acid itself (not acetylsalicylic acid) is a plant hormone but is toxic. A general principle: most bitter-tasting substances are often toxic.

Naming Acyl Groups

  • Acyl groups, derived from carboxylic acids by removing the hydroxyl group (\text{-OH}), are named by replacing the suffix \text{-ic} with either \text{-yl} or \text{-oyl}.

  • Exception: The acyl group for acetic acid is uniquely named an $acetyl$ group.

Dicarboxylic Acids

  • Definition: Compounds possessing two carboxyl (\text{-COOH}) groups.

  • Nomenclature: Named by adding \text{-dioic acid} to the corresponding alkane name.

Unsaturated Acids

  • Nomenclature: Named using the IUPAC system with the ending \text{-enoic}.

  • Example: \text{H}_2\text{C=CH-COOH} is named propenoic acid.

Worked Example 17.1: Naming a Multi-functional Compound

Compound A [Structure with \text{COOH}, \text{CH}_3 on \text{C2} and \text{OH} on \text{C3} of a $4$-carbon chain]

  • Analysis: This molecule contains both an alcohol and a carboxylic acid. Since carboxylic acids have higher priority, it is named as a carboxylic acid.

    • Identify the longest chain containing the \text{-COOH} group and number it starting with the carbonyl carbon ($1$).

  • Systematic Name: $3$-hydroxy-$2$-methylbutanoic acid

  • Common Name: $\beta$-hydroxy-$\alpha$-methyl-butyric acid

Compound B [Structure with \text{COOH}, \text{NH}_2 on \text{C2} and \text{OH} on \text{C3} of a $4$-carbon chain]

  • Systematic Name: $2$-amino-$3$-hydroxyl-butanoic acid

  • Common Name: $\alpha$-amino-$\beta$-hydroxyl-butyric acid

Acidity of Carboxylic Acids

Dissociation and Equilibria

  • Learning Objective: Understand the acidity of different carboxylic acids and predict products upon reaction with strong bases.

  • Dissociation: A carboxylic acid dissociates in solution to form a carboxylate anion (or carboxylate) and a proton (\text{H+}).

    • \text{R-COOH} \rightleftharpoons \text{R-COO}^- + \text{H}^+

  • Weak Acids: Carboxylic acids are classified as weak acids, establishing an equilibrium in aqueous solutions with their corresponding carboxylate anions.

  • Naming Carboxylate Anions: The name of a carboxylate anion is derived by replacing the \text{-ic} ending of the carboxylic acid with \text{-ate}.

Acid Strength Measurement: $Ka$ and $pKa$

  • Acid Dissociation Constant ($K_a$): Measures the comparative strength of an acid.

  • $pKa$ Value: Defined as \text{pKa} = -\text{log}{10}\text{Ka}. This logarithmic scale simplifies the comparison of acid strengths.

    • Stronger Acid: A smaller \text{pKa} value indicates a stronger acid.

    • Weaker Acid: A larger \text{pKa} value indicates a weaker acid.

    • Magnitude: A $1.0 \text{pKa} unit change represents a $10$-fold difference in the acidity of the molecule.

Table 17.2: Carboxylic Acid Dissociation Constants

Name

Structure of Acid

\text{Ka}

\text{pKa}

Trichloroacetic acid

\text{Cl}_3\text{CCOOH}

\text{2.3} \times 10^{-1}

0.64

Chloroacetic acid

\text{ClCH}_2\text{COOH}

\text{1.4} \times 10^{-3}

2.85

Formic acid

\text{HCOOH}

\text{1.8} \times 10^{-4}

3.74

Acetic acid

\text{CH}_3\text{COOH}

\text{1.8} \times 10^{-5}

4.74

Propanoic acid

\text{CH}3\text{CH}2\text{COOH}

\text{1.3} \times 10^{-5}

4.89

Hexanoic acid

\text{CH}3\text{(CH}2\text{)}_4\text{COOH}

\text{1.3} \times 10^{-5}

4.89

Benzoic acid

\text{C}6\text{H}5\text{COOH}

\text{6.5} \times 10^{-5}

4.19

Acrylic acid

\text{H}_2\text{C=CHCOOH}

\text{5.6} \times 10^{-5}

4.25

Oxalic acid

\text{HOOCCOOH}

\text{5.4} \times 10^{-2}

1.27

\text{^-OOCCOOH}

\text{5.2} \times 10^{-5}

4.28

Glutaric acid

\text{HOOC(CH}2\text{)}3\text{COOH}

\text{4.5} \times 10^{-5}

4.35

\text{^-OOC(CH}2\text{)}3\text{COOH}

\text{3.8} \times 10^{-6}

5.42

  • General Trend: Acidity generally correlates with the \text{pH} scale; stronger acids have lower \text{pKa} values (closer to $0$ or negative), while weaker acids have higher \text{pKa} values (closer to $14$). For context, chlorosulfuric acid (a super acid) has a \text{pKa} of approximately -4.

Neutralization Reactions

  • Carboxylic acids react with bases in a neutralization reaction to produce a neutral carboxylic acid salt (e.g., sodium acetate) and water (\text{H}_2\text{O}).

Worked Example 17.4: Acetic Acid vs. Trichloroacetic Acid Acidity

  • Problem: Explain why trichloroacetic acid is a stronger acid than acetic acid.

  • Structural Analysis: Both have a carbonyl carbon ($1$) and an alpha carbon ($2$).

    • Acetic Acid: The alpha carbon ($2$) is bonded to three hydrogen atoms.

    • Trichloroacetic Acid: The alpha carbon ($2$) is bonded to three chlorine atoms.

  • Electronegativity Effect (Inductive Effect):

    • Chlorine atoms are significantly more electronegative than hydrogen atoms.

    • In trichloroacetic acid, the three chlorine atoms pull electron density away from the alpha carbon ($2$). This electron-withdrawing effect is propagated through the molecule.

    • This withdrawal of electrons makes the carbonyl carbon ($1$) more electron-deficient. Consequently, the oxygen in the hydroxyl group (\text{-OH}) attached to the carbonyl carbon becomes less electron-rich (less \text{δ-}) and more \text{δ+}).

    • The O-H covalent bond is thereby weakened, requiring less energy for dissociation and making the hydrogen atom (\text{H+}) more easily released.

  • Conclusion: Trichloroacetic acid is a stronger acid because the electron-withdrawing chlorine atoms stabilize the conjugate base and make the proton easier to remove.

Reactions of Carboxylic Acids: Ester and Amide Formation

Overview of Formation Reactions

  • Learning Objective: Describe the formation of esters and amides from carboxylic acids.

  • The chemical reactions of carboxylic acids with alcohols (to form esters) and amines (to form amides) are fundamentally similar. Both involve a substitution of the hydroxyl group (\text{-OH}) from the carboxylic acid with an alcohol (\text{-OR}) or amine (\text{-NH}2) functional group, resulting in the formation of water (\text{H}2\text{O}).

Esterification

  • Process: Esterification is carried out by warming a carboxylic acid with an alcohol in the presence of a strong-acid catalyst, such as sulfuric acid (\text{H}2\text{SO}4).

  • Reversible Equilibrium: These reactions are reversible and typically reach an equilibrium where significant amounts of both reactants and products are present.

  • General Reaction: \text{R-COOH + R'-OH} \xrightarrow{\text{H}^+, \text{heat}} \text{R-COOR'} + \text{H}_2\text{O}

Worked Example 17.5: Formation of Wintergreen Oil

  • Problem: Wintergreen oil, an ester, is formed from ortho (o)-hydroxybenzoic acid (salicylic acid) and methanol. Determine the structure of the product.

  • Analysis Steps:

    1. Orient the reactants: Place the carboxylic acid's \text{-COOH} group facing the alcohol's \text{-OH} group.

    2. Eliminate water: Remove the \text{-OH} from the carboxylic acid and the \text{-H} from the alcohol's hydroxyl group to form \text{H}_2\text{O}.

      • (Side Note: In organic chemistry, $reactants$ are used, while in biological chemistry, $substrates$ are used.)

    3. Form the ester bond: Connect the remaining \text{-RCO} group from the acid to the \text{-OR} group from the alcohol via a covalent bond.

  • Solution: Ortho-hydroxybenzoic acid + Methanol \rightarrow Methyl salicylate + \text{H}_2\text{O}.

Amide Formation

  • Unsubstituted Amides: Formed by the reaction of a carboxylic acid with ammonia (\text{NH}_3).

    • \text{R-COOH + NH}3 \rightarrow \text{R-CONH}2 + \text{H}_2\text{O}

  • Substituted Amides: Formed by the reaction of carboxylic acids with primary amines (\text{R'NH}_2) or secondary amines (\text{R'R''NH}).

    • \text{R-COOH + R'NH}2 \rightarrow \text{R-CONHR'} + \text{H}2\text{O}

    • \text{R-COOH + R'R''NH} \rightarrow \text{R-CONR'R''} + \text{H}_2\text{O}

  • Tertiary Amines and Amide Formation: Tertiary amines (e.g., triethylamine) do not form amides with carboxylic acids. This is because they lack a hydrogen atom bonded to the nitrogen atom, which is necessary to form a water molecule (\text{H}_2\text{O}) as a byproduct. Instead, tertiary amines can only form ammonium salts with carboxylic acids.

Hydrolysis of Esters and Amides

Reversing Formation Reactions

  • Learning Objective: Predict the hydrolysis products of esters and amides.

  • General Principle: Esters and amides can undergo hydrolysis to yield carboxylic acids. Esters produce alcohols, while amides produce amines. These reactions are essentially the reverse of their formation.

  • Mechanism: Hydrolysis involves a hydrogen atom ($\text{-H}) and a hydroxyl group ($\text{-OH}) from a water molecule ($\text{H}_2\text{O}) breaking the covalent bond. This process follows the carbonyl-group substitution pattern.

Hydrolysis of Esters

  • Net Effect: The \text{-OR'} group of the ester is replaced by an \text{-OH} group, resulting in a carboxylic acid. The released \text{-OR'} group combines with the \text{-H} from water to form an alcohol ($\text{R'-OH}).

  • General Reaction: \text{R-COOR'} + \text{H}_2\text{O} \rightarrow \text{R-COOH} + \text{R'-OH}

  • Acid-catalyzed hydrolysis: This is simply the reverse of the esterification reaction.

  • Base-catalyzed hydrolysis (Saponification): Hydrolysis performed using a strong base like sodium hydroxide (\text{NaOH}) or potassium hydroxide ($\text{KOH}) is called saponification. This process is important in soap making.

Worked Example 17.7: Ethyl Formate Hydrolysis

  • Problem: Predict the products of an acid-catalyzed hydrolysis reaction of ethyl formate (a flavor constituent of rum).

  • Analysis: The name "ethyl formate" indicates the products: ethyl alcohol and formic acid.

    • Write the ester structure and locate the bond between the carbonyl carbon and the \text{-OR'} group.

    • Break this bond and add \text{-OH} to the carbonyl carbon (forming the carboxylic acid) and \text{-H} to the \text{-OR'} group (forming the alcohol).

  • Solution: Ethyl formate ($\text{H-COOCH}2\text{CH}3) + \text{H}2\text{O} \xrightarrow{\text{H}^+} Formic acid ($\text{H-COOH}) + Ethyl alcohol ($\text{HOCH}2\text{CH}_3).

Hydrolysis of Amides

  • Stability: Amides are stable in water under normal conditions.

  • Conditions for Hydrolysis: Amide hydrolysis can occur with heating, facilitated by either acids or bases.

    • Acid Hydrolysis: Produces a carboxylic acid and a protonated amine.

      • \text{R-CONHR'} + \text{H}2\text{O} + \text{H}^+ \rightarrow \text{R-COOH} + \text{R'NH}3^+

    • Base Hydrolysis: Produces a carboxylate anion and an amine.

      • \text{R-CONHR'} + \text{H}2\text{O} + \text{OH}^- \rightarrow \text{R-COO}^- + \text{R'NH}2

  • Physiological Relevance: The different forms of products (protonated amine in acid, free amine in base; carboxylic acid in acid, carboxylate in base) highlight the influence of \text{pH} on chemical reactions in biological systems, which is critical for understanding amino acid reactions at physiological \text{pH} (approximately \text{7.4}).

Worked Example 17.8: N-Ethylbutanamide Hydrolysis

  • Problem: Identify the carboxylic acid and amine produced after the hydrolysis of N-ethylbutanamide.

  • Solution: N-ethylbutanamide + \text{H}_2\text{O} \rightarrow Butanoic acid + Ethylamine.

Phosphoric Acid Derivatives

Phosphate Esters

  • Learning Objective: Recognize and draw the structures of phosphate esters and their ionized forms.

  • Definition: A phosphate ester is a compound formed by the reaction of an alcohol with phosphoric acid.

  • Phosphoric Acid (\text{H}3\text{PO}4):

    • An inorganic acid that bears some structural resemblance to a carboxylic acid.

    • Possesses three acidic hydrogen atoms, enabling it to undergo serial dissociations to form three different anions (\text{H}2\text{PO}4^-, \text{HPO}4^{2-}, \text{PO}4^{3-}), eventually yielding a phosphate ion.

  • Formation of Phosphate Esters: Similar to carboxylic acids, phosphoric acid reacts with alcohols. The R-group of an alcohol (\text{CH}_3\text{O-}) can substitute for one, two, or all three of the hydroxyl ($\text{-OH}) groups of phosphoric acid to form phosphate mono-esters, di-esters, or tri-esters, respectively.

  • Acidity of Phosphate Esters: Phosphate mono-esters and di-esters remain acidic because they still possess dissociable hydrogen atoms.

  • Anionic Forms: In neutral or alkaline solutions, phosphate esters are predominantly present as anions (e.g., \text{-PO}_3^{2-}).

  • Phosphoryl Group: The \text{-PO}_3^{2-} group is known as a phosphoryl group.

Polyphosphoric Acids and Their Esters

  • Di-phosphoric Acid (Pyrophosphoric Acid) and Tri-phosphoric Acid: These complex acids are formed when two or three molecules of phosphoric acid combine, with a loss of water (\text{H}_2\text{O}$$) through an anhydride linkage.

  • Anhydride: A molecule that undergoes a dehydration reaction (loss of a water molecule) resulting in the formation of an ester or anhydride bond.

  • Di-phosphates and Tri-phosphates: These are the esters formed from the corresponding anhydride-containing di-phosphoric and tri-phosphoric acids.

Phosphorylation: Biological Significance

  • Definition: Phosphorylation is the transfer of a phosphoryl group from one molecule to another.

  • Metabolic Energy: This process is central to "intermediary metabolism" and the "energy of life."

    • In metabolism, phosphoryl groups are supplied by adenosine triphosphate (ATP). The energy-releasing reactions involve the conversion of ATP to adenosine diphosphate (ADP), and then to adenosine monophosphate (AMP).

  • Molecular Regulation: The addition and removal of phosphoryl groups are common mechanisms for regulating the function of molecules, particularly proteins.

    • Proteins are often phosphorylated on specific amino acids such as serine, threonine, and tyrosine to modulate their activity (e.g., as studied by Dr. Edwin Krebs, Nobel Prize $1992$, for metabolic energy regulation).

Organic Functional Groups Concept Map

  • A comprehensive map categorizes organic compounds based on their functional groups, illustrating the hierarchical relationships and interconversions. (Visual representation not directly translatable to text, but implies a tree or flow chart structure)

  • Key Divisions:

    • Single bonds only: Alkanes, Alkyl halides.

    • Multiple bonds: Alkenes, Alkynes, Aromatics.

    • Oxygen, Nitrogen, Sulfur present:

      • No C=O: Alcohols, Phenols, Ethers, Thiols, Disulfides, Amines.

      • C=O present (carbonyl):

        • No single bond O or N connected to C=O: Aldehydes (H attached to C=O), Ketones (No H attached to C=O).

        • Single bond O or N connected to C=O: Carboxylic Acids (-OH attached), Esters (-OR attached), Amides (-NH2, -NHR', -NR'2 attached), Anhydrides.